Cardiovascular disease is the leading cause of death in most developed countries in the world. About half of all deaths from coronary heart disease are sudden and unexpected, regardless of the underlying disease. Approximately one million individuals in the U.S. develop conditions each year that place them at high risk for sudden cardiac death (SCD). About 450,000 SCDs occur each year among U.S. adults. Sudden Cardiac Arrest (SCA), the cause of SCD, is fatal in approximately 95% of cases. SCA often results from ventricular fibrillation (VF), which causes cardiac output to decrease nearly to zero, a level that causes irreversible damage to the brain and other organs within 10 min or less. Related to this fact, the odds of surviving SCA decrease approximately 10% for every minute the individual remains in VF before defibrillation is successfully performed. Patients at high risk for SCD may be implanted with an implantable cardioverter defibrillator (ICD) to provide life-saving defibrillation shocks in the event of the onset of a life-threatening cardiac arrhythmia. Approximately 150,000 patients receive ICD implantations each year in the U.S.
Current ICDs use high-energy (25-35 J) shocks to terminate VF. While large truncated exponential biphasic shocks used by modern devices are effective at terminating VF, the high current density surrounding shocking electrodes may cause tissue damage that leads to increased morbidity and mortality. This damage may be caused by electroporation, which leads to conduction disturbances, tissue stunning, necrosis, and compromised cardiac function. ICD shocks have been associated with elevated troponin I levels, a well-known marker of cardiac cell death. ICD patients that receive shocks are at an increased risk of death, even when shocks were delivered inappropriately for causes other than life-threatening arrhythmias. However, there is no increase in mortality risk in patients that received antitachycardia pacing but no shocks.
Severe mental distress and lower quality of life scores accompany many patients that receive defibrillation shocks. If a patient does not lose consciousness before a shock is delivered, large energy shocks cause severe pain. While ICD defibrillation shock strengths are often set at maximum levels of 35 J, shocks as low as 0.4 J are reported as painful. Inappropriate shocks are delivered to 11-13% of patients and the shocks are often delivered without warning. These patients are at increased risk for anxiety, stress, and possibly post-traumatic stress disorder.
ICDs charge a large capacitor to deliver defibrillation shocks, often up to hundreds of volts. Patients that receive multiple high-energy shocks deplete the battery of the ICD more rapidly, requiring expensive and invasive device replacement surgery. Development of reliable low energy defibrillation techniques will reduce the device size and prolong the battery life.
ICDs do not prevent the arrhythmias from occurring, but rather rapidly detect and treat the arrhythmias using electrical stimulation. Since the introduction of the ICD more than three decades ago, numerous improvements have been made to lower the energy required for cardioversion. Improvements to battery life and integrated electronics have shrunk the size of ICDs while increasing the longevity of the devices. Antitachycardia pacing (ATP) for ventricular tachycardia has reduced the number of shocks given for monomorphic VT episodes. However, ATP is not effective for VF. Biphasic shocks reduce the energy requirements and increase the success rates of defibrillation shocks. Alternate waveform shapes have had limited success in lowering defibrillation thresholds (DFTs), but have not been widely adopted and require shocks of sufficient amplitude that they cause damage and pain.
The critical mass theory of defibrillation states that for a defibrillation shock to be successful, a shock must render a critical mass (usually 75-90% of the ventricles) of the ventricular tissue unexcitable by activation or extension of the refractory period. Capturing large sections of cardiac tissue at sites distant from shocking electrodes is necessary to capture a critical mass of the heart and to terminate reentrant circuits that perpetuate VF. Cardiac mapping efforts during defibrillation have demonstrated that defibrillation attempts using a right ventricular electrode often fail because waves of activation emerge from the left ventricular apex region. This area of the left ventricle often has relatively low current density during the defibrillation shock. Several studies have explored the use of an auxiliary shock delivered to the LV electrode. Other studies have included the LV electrode as an additional path for current in parallel with other standard clinical locations. Since the LV electrode effectively spreads current into this area of low current density, DFTs drop significantly. While these techniques have lowered DFTs by as much as 50% or more, the DFTs are often still an order of magnitude above the pain threshold. Sequential pulses delivered through multiple pathways have not gained clinical acceptance due to additional complexity and risk associated with implantation of additional leads.
There has been a resurgence of interest and research into low energy multi-pulse and high frequency defibrillation techniques. These techniques generally fall into one of two categories: 1) A series of pacing pulses or low energy shocks delivered near or just below the intrinsic VF cycle length that progressively capture a larger and larger region of fibrillating tissue until VF is halted.22, 52-61 or 2) High frequency (50-1000 Hz) stimulation that blocks all activation in a critical mass so that reentrant circuits are disrupted and VF halts.
As with standard defibrillation shocks, low energy defibrillation techniques rely on far field virtual electrode polarization to create secondary sources that disrupt reentrant circuits to terminate VF. Traditional defibrillation shocks require a minimum field gradient of 2.7-10.9 V/cm throughout the heart for successful defibrillation. Intracardiac shocking coils, as used by ICDs, do not create an even field distribution throughout the heart. High current densities near shocking coils lead to field gradients more than 20 times the field gradient experienced by regions of the heart far from the shocking coils. While the field gradients required for multi-pulse techniques may be as low as 250 mV/cm, to create this field strength at sites distant from the shocking electrodes, much higher field gradients are required close to the shocking coils. Low energy multi-pulse techniques have been effective in simulations with even field gradients and in experimental configurations with rabbit or guinea pig ventricles or canine atria, but the energy required to defibrillate large, fibrillating ventricles with secondary sources at sites far from the stimulating electrodes will require substantial increases in energy and field gradient to create virtual electrodes at remote sites. Successful demonstration of low energy multi-pulse techniques in large hearts may prove difficult because direct local capture leads to a limited region of captured tissue, much smaller than a critical mass of the heart. While shocks from ICDs are the only effective therapy for VF, shocks may cause damage to tissue surrounding intracardiac electrodes leading to increased risk of arrhythmia or death. While the extent of the damage caused by shocks is controversial, shocks delivered while patients are conscious result in pain, anxiety, and lower quality of life measures.